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Bitter Cactus
reformed bad boy


Registered: 01/26/12
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Re: How dangerous do you guys feel MDMA truly is? [Re: 404]
#22079219 - 08/11/15 11:04 PM (8 years, 5 months ago) |
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Quote:
404 said:
Quote:
Gottaloveacid said:
Quote:
Gresh said: while ive never used MDMA, ive always put it on par with meth. which doesnt eat holes in your brain, contrary to pop culture
meth tends to be more destrictive overall, obviously, but i'm talking on a dose-by-dose, mg-for-mg basis
the only reason ive avoided MDMA is because i have problems with dissociation/depersonalization anxiety. despite mdma's lovey dovey reputation, it has a tendency to trigger DP
MDMA and Meth are neurotoxic in almost the exact same way, only difference is MDMA is toxic to serotonin and meth to dopamine.
source?
I think they are neurotoxic to both.
IV meth and MDMA feel nearly the same in every way but the meth is a thousand times more intense and pleasurable at the peak.
-------------------- Taking acid and thinking you are a better man is a lot different then actually becoming a better man.
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Gottaloveacid
Weedbass



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Posts: 3,421
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Re: How dangerous do you guys feel MDMA truly is? [Re: 404]
#22079249 - 08/11/15 11:10 PM (8 years, 5 months ago) |
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It's just common sense on how these drugs work (releasing agents)
All is fine and dandy until it releases the last of a neurotransmitter and then another neurotransmitter flood in place, creating oxidizing free radicals. Since meth is one of the more powerful dopamine releasing agents, that is why it has a lot of documented cases of neurotoxicity. People who take it for days on end run out of dopamine but they still have meth in their systems, and that causes damage just like MDMA would.
Quote:
Bitter Cactus said:
I think they are neurotoxic to both.
IV meth and MDMA feel nearly the same in every way but the meth is a thousand times more intense and pleasurable at the peak.
I am not sure if meth acts on serotonin, but I know MDMA works on both dopamine and serotonin(both also work on norepinephrine as well). MDMA can cause dopamine neurotoxicity if taken in extreme doses because it is a mild dopamine releasing agent. If I had to guess, by the time you started to experience dopamine neurotoxicity from MDMA on the same level as serotonin, you would be long dead from overdose.
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 The greatest story ever told is the story that never ends! wubba lubba dub dubstep
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404
error


Registered: 08/20/10
Posts: 14,539
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Re: How dangerous do you guys feel MDMA truly is? [Re: Bitter Cactus]
#22079252 - 08/11/15 11:11 PM (8 years, 5 months ago) |
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http://www.ncbi.nlm.nih.gov/pubmed/11351932
MDMA is not neurotoxic when directly injected into the brain, even after stimulating 5ht release.
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MagicalOrangutan
Curious Cat



Registered: 06/29/12
Posts: 3,538
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Re: How dangerous do you guys feel MDMA truly is? [Re: Gottaloveacid]
#22079256 - 08/11/15 11:13 PM (8 years, 5 months ago) |
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Can we all just agree that recreational stimulants, mdma etc, all just cause excited release of "feel good" neurotransmitters and that such a thing is fucking stupid unless done on special occasions to enhance the situation?
-------------------- On the ground you lay, with your dogs you pray, at a neon hieroglyph sky you gaze Hugging your mind, praying to survive, feeling the love of the hieroglyphs in the sky We all need more love, and mainly less hate Hate is the blind that covers the heart's eye That makes the heart's eye cry Locked deep away in the skies of our minds It's all in the mind
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Bitter Cactus
reformed bad boy


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Re: How dangerous do you guys feel MDMA truly is? [Re: MagicalOrangutan]
#22079262 - 08/11/15 11:14 PM (8 years, 5 months ago) |
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Meth at higher doses one thousand percent releases a ton of serotonin. It feels nearly identical to mdma to me.
-------------------- Taking acid and thinking you are a better man is a lot different then actually becoming a better man.
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Rebelutionsssss
Mdmazing



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Re: How dangerous do you guys feel MDMA truly is? [Re: Bitter Cactus]
#22079275 - 08/11/15 11:17 PM (8 years, 5 months ago) |
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But is far more addictive and causes more damage in the persons life.
-------------------- : To define is to confine.
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Gottaloveacid
Weedbass



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Re: How dangerous do you guys feel MDMA truly is? [Re: Bitter Cactus]
#22079279 - 08/11/15 11:18 PM (8 years, 5 months ago) |
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I will read that article tomorrow since I am about to hit the hay, but did the study say whether or not the MDMA was active when injected directly into the brain? MDMA isn't dangerous unless it actually reaches a substantial blood plasma level (ie the level it becomes pharmacologically active)Quote:
MagicalOrangutan said: Can we all just agree that recreational stimulants, mdma etc, all just cause excited release of "feel good" neurotransmitters and that such a thing is fucking stupid unless done on special occasions to enhance the situation?
It all depends on what drugs you're taking. Strong neurotransmitter releasers like methampthetamine and mdma are the only ones I would worry about. Normal amphetamine is no where near as toxic as it releases much less dopamine than meth. That is why they can give it to children and no one ever talks about how it can "kill brain cells"Quote:
Bitter Cactus said:
Meth at higher doses one thousand percent releases a ton of serotonin. It feels nearly identical to mdma to me.
Is that just your opinion or can someone actually link something that says how effective of a serotonin releaser meth actually is? Actually it doesn't really even matter, my whole point was that these releasing agents are all neurotoxic.
I have had dexamp feel like MDMA just take orally. The tactile sensations and overwhelming empathy weren't there, but euphoria and mood wise it felt the exact same at times
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 The greatest story ever told is the story that never ends! wubba lubba dub dubstep
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404
error


Registered: 08/20/10
Posts: 14,539
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Re: How dangerous do you guys feel MDMA truly is? [Re: Gottaloveacid]
#22079289 - 08/11/15 11:21 PM (8 years, 5 months ago) |
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yes, it said
Quote:
CONCLUSIONS:
These data demonstrate that MDMA when injected directly into the brain produces 5-HT release but no neurotoxicity, suggesting that it must be metabolised peripherally in order to produce compounds that induce free radical formation and neurotoxicity in the brain.
so pretty much it is the metabolism of mdma (and mda) that is responsible for its neurotoxicity.
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Sophistic Radiance
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Re: How dangerous do you guys feel MDMA truly is? [Re: 404]
#22079305 - 08/11/15 11:28 PM (8 years, 5 months ago) |
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Dopamine is far more poisonous than serotonin... as a molecule, it's relatively smaller than serotonin, and it has two adjacent hydroxy groups, which make it more polar and more disruptive to intermolecular bonds, especially in high concentrations. Hydrogen bonds with sulfur and oxygen are integral to protein structure and dopamine's strong electronegativity really fucks that shit up, partially denaturing all proteins comprising the cell exposed to it in high concentration. Like dissolves like, and dopamine is like to the chemical bonds that hold cells intact.
This is why MDMA causes so much less brain damage and addiction than meth, even though its potency as a serotonin releasing agent is comparable to meth's potency as a dopamine releasing agent. I'm guessing that the dopaminergic oxidative stress of acute meth intoxication, and its tendency to completely fuck up the neurons exposed to that much dopamine, is responsible for the rapid occurrence of drug-craving, as the user feels compelled to compensate for the paradoxical loss of dopamine reuptake in their dopamine-flooded synapses by releasing even more dopamine throughout the lesser-damaged areas of the brain. By comparison, serotonin toxicity merely damages the electrical synapses associated with serotonin receptors, causing a loss of serotonergic response without the loss of serotonin reuptake.
-------------------- Enlil said: You really are the worst kind of person.
Edited by Sophistic Radiance (08/11/15 11:55 PM)
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Rebelutionsssss
Mdmazing



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This is an old documentary but it's definitely cool to watch. Came out when MDMA started getting really well known
-------------------- : To define is to confine.
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Gottaloveacid
Weedbass



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Re: How dangerous do you guys feel MDMA truly is? [Re: 404]
#22079383 - 08/11/15 11:47 PM (8 years, 5 months ago) |
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Quote:
404 said: yes, it said
Quote:
CONCLUSIONS:
These data demonstrate that MDMA when injected directly into the brain produces 5-HT release but no neurotoxicity, suggesting that it must be metabolised peripherally in order to produce compounds that induce free radical formation and neurotoxicity in the brain.
so pretty much it is the metabolism of mdma (and mda) that is responsible for its neurotoxicity.
I am curious, did it at all say how much serotonin they estimated to be released (versus a normal dose of oral mdma)? If it listed blood plasma levels, it would be best. Metabolism of MDMA is NOT the currently accepted view on it's neurotoxicity, rather it has been shown it is the dopamine entering the serotonin axons when levels plummet to compensate for missing serotonin, which as blindsophist said, dopamine is a very toxic molecule. When that happens, the dopamine and mao react (if I am not mistaken) to create dangerous free radicals. It has nothing to do with metabolism in normal oral doses according to current medical literature. Keep in mind, that paper was published over 14 years ago and literature following the model I just explained is much more current/abundant. Not trying to discredit the study, I just think they discovered more of a fluke than anything actually meaningful
To me it sounds like that study just shows it is possible for MDMA to not be neurotoxic (or at least not to an extent that is measurable) if the amount is low. Without blood plasma levels in the study to compare to normal oral/iv MDMA dosages, I am forced to assume that it could be possible that whatever they were testing on just didn't have enough MDMA active to cause measurable damage. I would have to see the full article rather than the abstract just to be certain though.
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 The greatest story ever told is the story that never ends! wubba lubba dub dubstep
Edited by Gottaloveacid (08/11/15 11:54 PM)
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Sophistic Radiance
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Re: How dangerous do you guys feel MDMA truly is? [Re: Gottaloveacid]
#22079423 - 08/11/15 11:59 PM (8 years, 5 months ago) |
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Wow, so dopamine is still responsible for MDMA neurotoxicity? Kinda tells you something about a drug that directly floods the brain with dopamine. If MDMA is a bic lighter, methamphetamine is a blowtorch.
-------------------- Enlil said: You really are the worst kind of person.
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404
error


Registered: 08/20/10
Posts: 14,539
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Quote:
BlindSophist said: Dopamine is far more poisonous than serotonin... as a molecule, it's relatively smaller than serotonin, and it has two adjacent hydroxy groups, which make it more polar and more disruptive to intermolecular bonds, especially in high concentrations. Hydrogen bonds with sulfur and oxygen are integral to protein structure and dopamine's strong electronegativity really fucks that shit up, partially denaturing all proteins comprising the cell exposed to it in high concentration. Like dissolves like, and dopamine is like to the chemical bonds that hold cells intact.
This is why MDMA causes so much less brain damage and addiction than meth, even though its potency as a serotonin releasing agent is comparable to meth's potency as a dopamine releasing agent. I'm guessing that the dopaminergic oxidative stress of acute meth intoxication, and its tendency to completely fuck up the neurons exposed to that much dopamine, is responsible for the rapid occurrence of drug-craving, as the user feels compelled to compensate for the paradoxical loss of dopamine activity in their busted-up dopamine-flooded synapses by releasing even more dopamine. By comparison, serotonin toxicity merely damages the electrical synapses associated with serotonin receptors, causing a reduction in serotonergic response without the destruction of serotonin receptors or their host cells.
very interesting stuff, though i think you meant to edit that last sentence in the first paragraph further.
i am now looking into the Vesicular Monoamine Transporter 2 (VMAT2) and it's role in these drugs. it seems cocaine damages these connections in the ventral striatum (reward pathway between the forebrain and nucleus accumbens and another part) and meth/amphetamine disable it by binding to the Tetrabenazine site, which i'm guessing has something to do with the two ch3 parts on the back of both molecules?
tetrabenazine

meth

isn't that how meth "turns off" dopamine receptors in a way, considering this protein is responsible for shuttling catecholamines into their respective synapses?
brainz r so kewl
please correct me if i am wrong
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Rebelutionsssss
Mdmazing



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Re: How dangerous do you guys feel MDMA truly is? [Re: 404]
#22079440 - 08/12/15 12:04 AM (8 years, 5 months ago) |
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I've wanted a discussion like this for so long. So some of the damage comes from the brain trying to counteract the missing serotonin by flooding the empty receptors with dopamine thus causing damage to them?
-------------------- : To define is to confine.
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404
error


Registered: 08/20/10
Posts: 14,539
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Re: How dangerous do you guys feel MDMA truly is? [Re: Gottaloveacid]
#22079457 - 08/12/15 12:08 AM (8 years, 5 months ago) |
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no offense, and your points may very well be valid. but why are you asking me these questions when you said you were going to bed? if you find something worth mentioning that would fully discredit what it says, i would very much like to know how and why so i can stop citing it. i tend to overlook the finer details of research documents when reading over them.
Quote:
Rebelutionsssss said:
I've wanted a discussion like this for so long. So some of the damage comes from the brain trying to counteract the missing serotonin by flooding the empty receptors with dopamine thus causing damage to them?
I'm not sure i can fully answer that as i am still learning myself, PED would probably know.
what makes you ask this question though?
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Gottaloveacid
Weedbass



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Re: How dangerous do you guys feel MDMA truly is? [Re: 404] 1
#22079468 - 08/12/15 12:10 AM (8 years, 5 months ago) |
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Well, I don't know if I would say that. A single MDMA dose will be much more toxic than a single meth dose, even though the meth lasts twice as long. You will run out of serotonin very quickly, and that is when the damage mostly happens. If you don't overdue the meth, I highly doubt you will run out of dopamine. The damage from meth due to neurotoxicity is usually more severe than with MDMA (I guess you could say the dopamine system is a little bit more useful than the serotonin system in day to day life), but you only start to see it in long term users. It's when you start doing it every day, multiple days in a row, high doses, etc that the dopamine system starts to wear down.
Quote:
Rebelutionsssss said:
I've wanted a discussion like this for so long. So some of the damage comes from the brain trying to counteract the missing serotonin by flooding the empty receptors with dopamine thus causing damage to them?
Exactly. It doesn't help that MDMA is also a mild dopamine releasing agent, and if you combine MDMA with meth or speed you are significantly increasing neurotoxicity.
This page explains in simple words exactly what happens
https://dancesafe.org/drug-information/ecstasy-slideshow/
Quote:
404 said: no offense, and your points may very well be valid. but why are you asking me these questions when you said you were going to bed? if you find something worth mentioning that would fully discredit what it says, i would very much like to know how and why so i can stop citing it. i tend to overlook the finer details of research documents when reading over them.
Quote:
Rebelutionsssss said:
I've wanted a discussion like this for so long. So some of the damage comes from the brain trying to counteract the missing serotonin by flooding the empty receptors with dopamine thus causing damage to them?
I'm not sure i can fully answer that as i am still learning myself, PED would probably know.
what makes you ask this question though?
You guys got my interest now haha. Sadly the abstract doesn't provide enough details, so without reading the whole thing I won't know for sure
Basically I am just concerned the study didn't test exactly how much MDMA was in the test animal's blood to know if the results from the test were just caused by a low dose or whether or not they were actually on to something. It is extremely difficult to deliver a correct dose of a drug injected directly into the brain.
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 The greatest story ever told is the story that never ends! wubba lubba dub dubstep
Edited by Gottaloveacid (08/12/15 12:19 AM)
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Rebelutionsssss
Mdmazing



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Re: How dangerous do you guys feel MDMA truly is? [Re: 404]
#22079485 - 08/12/15 12:15 AM (8 years, 5 months ago) |
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and a few major study's citing neurotoxicity I've read have just been completely unrealistic with their dosing regiments. Injecting monkeys multiple times a day every day with grams of MDMA for months at a time. Yea no fucking shit there's going to be severe toxicity to the animals brain.
-------------------- : To define is to confine.
Edited by Rebelutionsssss (08/12/15 12:16 AM)
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Gottaloveacid
Weedbass



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Re: How dangerous do you guys feel MDMA truly is? [Re: 404]
#22079500 - 08/12/15 12:20 AM (8 years, 5 months ago) |
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Quote:
404 said: http://www.ncbi.nlm.nih.gov/pubmed/11351932
MDMA is not neurotoxic when directly injected into the brain, even after stimulating 5ht release.
Here are some (older) quotes that I dug up
Looking at past studies, it is clear that dopamine plays a crucial role in MDMA neurotoxicity. For example, in 1988, it was discovered that pre-treating rats with a-methyl-p-tyrosine, a substance that inhibits the synthesis of dopamine, prevents MDMA neurotoxicity (Stone et al., 1988). Also, in 1990 another study showed that if you destroy all of the rat’s dopamine terminals before giving them MDMA (thus eliminating all their dopamine), they sustain no serotonin axon loss (Schmidt et al., 1990). That same year they discovered that if you give the rats L-DOPA, a dopamine precursor, they sustain more neurotoxic damage when given MDMA. And a 1991 study demonstrated a linear correlation between the amount of dopamine release and the extent of MDMA-induced axon loss in rats (Nash and Nichols, 1991).
In 1987, researchers discovered that MDMA releases dopamine (Schmidt et al., 1987, Steele et al., 1987). Then, they discovered in 1996 that serotonin release also increases dopamine release (Gudelsky and Nash, 1996). This occurs because one of the serotonin receptors (receptor 2A), when activated by serotonin, stimulates the synthesis and release of dopamine (Nash, Schmidt et al., 1990). Also, drugs that block the 2A-receptor have been shown to reduce extracellular dopamine levels.
They further discovered that the uptake of dopamine into the serotonin terminal also occurs (Faraj et al., 1994), and that the terminal dose, in fact, contains a type of MAO known to metabolize dopamine (MAO-B). To further support the theory, in 1995 they discovered that MAO-B inhibitors (L-deprenyl or MDL-72974) reduce neurotoxic damage in rats given 40mg/kg of MDMA.
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 The greatest story ever told is the story that never ends! wubba lubba dub dubstep
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mollymadman
love each other :)

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Re: How dangerous do you guys feel MDMA truly is? [Re: Gottaloveacid]
#22079512 - 08/12/15 12:24 AM (8 years, 5 months ago) |
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All I can say is that I do MDMA about once a week and I'm fine. You feel shitty for a few days but you just gotta sleep for a day and youll be fine. I usually dose about 300-400mg when I do it over the course of a night. Sometimes less tho. Tolerance sucks.
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  Finding the answer... Finding that there ain't no answer to find.
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Sophistic Radiance
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Re: How dangerous do you guys feel MDMA truly is? [Re: Rebelutionsssss]
#22079515 - 08/12/15 12:24 AM (8 years, 5 months ago) |
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This thread got really interesting. Food for thought...
I tend to think of molecular chemistry in terms of electronegativity... meth is smaller and more polar than tetrabenazine, so it would rapidly accumulate in the tetrabenazine receptors and physically block off tetrabenazine itself. This would have more to do with the small size and localized electronegativity of meth, with its single secondary amine group, compared with the more broadly-distributed electronegativity and sheer bulk of tetrabenazine, with its aromatic ether bonds offsetting its ketone making it a weak agonist for VMAT2 compared with meth.
I'm at the point where I'm basically talking out of my ass but it sure is interesting all the same.
-------------------- Enlil said: You really are the worst kind of person.
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